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Mol Biol Cell. 2016 Sep 28. pii: mbc.E16-05-0318. [Epub ahead of print]

Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice.

Author information

1
Department of Gastroenterology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China, 430030 Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.
2
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.
3
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298 Department of Dermatology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China, 430030.
4
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298 School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei, 430065.
5
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
6
Department of Biology, Randolph-Macon College, Ashland, VA 23005.
7
Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln, Urbana, IL 61802-6199.
8
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298 zhibing.zhang@vcuhealth.org.

Abstract

Intraflagellar transport (IFT) is a conserved mechanism thought to be essential for the assembly and maintenance of cilia and flagella. However, little is known about its role in mammalian sperm flagella formation. To fill this gap, we disrupted the Ift20 gene in male germ cells. Homozygous mutant mice were infertile with significantly reduced sperm counts and motility. In addition, abnormally shaped elongating spermatid heads and bulbous round spermatids were found in the lumen of the seminiferous tubules. Electron microscopy revealed increased cytoplasmic vesicles, fiber-like structures, abnormal accumulation of mitochondria and a decrease in mature lysosomes. The few developed sperm had disrupted axonemes and some retained cytoplasmic lobe components on the flagella. ODF2 and SPAG16L, two sperm flagella proteins failed to be incorporated into sperm tails of the mutant mice, and in the germ cells, both were assembled into complexes with lighter density in the absence of IFT20. Disrupting IFT20 did not significantly change expression levels of IFT88, a component of IFT-B complex, and IFT140, a component of IFT-A complex. Even though the expression level of an autophagy core protein that associates with IFT20, ATG16, was reduced in the testis of the Ift20 mutant mice, expression levels of other major autophagy markers, including LC3 and ubiquitin were not changed. Our studies suggest that IFT20 is essential for male fertility and spermiogenesis in mice, and its major function is to transport cargo proteins for sperm flagella formation. It also appears to be involved in removing excess cytoplasmic components.

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